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AzTrials

Complex Endometrial Hyperplasia With AtypiaPhase 2feMMeNCT01686126

Improving the Treatment for Women With Early Stage Cancer of the Uterus

A Phase 2 study testing Levonorgestrel and Metformin in people with Complex Endometrial Hyperplasia With Atypia and Grade 1 Endometrial Endometrioid Adenocarcinoma, run by Queensland Centre for Gynaecological Cancer at 17 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

Currently the standard treatment for early stage endometrial cancer or endometrial hyperplasia with atypia is a total hysterectomy (an operation to remove the uterus) and removal of both ovaries. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Levonorgestrel and Metformin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
165 participants
Where
17 sitesin 2 countries
Study dates
Dec 2012to Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Females with a BMI > 30 kg/m2 wishing to retain fertility or females who are at high risk of surgical complications due to co-morbidities or obesity
  • Over 18 years of age at time of randomisation
  • Histologically confirmed complex endometrial hyperplasia with atypia or grade 1 endometrioid endometrial adenocarcinoma on a curette or endometrial biopsy
  • CT or MRI scan of pelvis, abdomen and chest (or chest X-Ray) suggesting the absence of extrauterine disease
  • Myometrial invasion on MRI of not more than 50%, for women with histologically confirmed Endometrial Cancer only (for women who are unable to fit into an MRI machine inclusion into trial is at investigators discretion)
  • No lymph vascular invasion on curetting or pipelle, if able to be assessed on sample
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  • Serum CA125 ≤ 30 U/mL
  • No hypersensitivity or contraindications for Mirena
  • Ability to comply with endometrial biopsies at specified intervals
  • Negative serum or urine pregnancy test in pre-menopausal women and women < 2 years after the onset of menopause
  • Creatinine < 150µmol/L (1.7 mg/dL) to be randomised into Mirena + Metformin arm (can still be eligible to be randomised to Mirena only or Mirena + Weight Loss, see section 5.4 Other Eligibility Criteria Considerations)

Who cannot join

  • ECOG performance status > 3
  • Grade 1 endometrioid adenocarcinoma of the endometrium with myometrial invasion deeper than 50% on MRI or any patients with grade 2 or grade 3 endometrioid adenocarcinoma
  • Histological (cell) type other than endometrioid adenocarcinoma (sarcomas or high risk endometrial e.g. papillary serous, clear cell)
  • Pregnant or planning to become pregnant during trial period
  • Has had prior treatment or undergoing current treatment for EAC or EHA
  • Patients with a history of pelvic or abdominal radiotherapy
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  • Unwilling to have additional endometrial biopsies or curettes and unable to attend three monthly clinical assessments
  • Unable to provide informed consent
  • Unable or unwilling to complete questionnaires
  • Evidence of extrauterine spread on medical imaging
  • Congenital or acquired uterine anomaly which distorts the uterine cavity
  • Acute pelvic inflammatory disease
  • Conditions associated with increased susceptibility to infections with microorganisms (e.g., AIDS, leukaemia, IV drug abuse) according to the patients Medical History
  • Genital actinomycosis
  • Current other cancer, except low grade malignancies that do not require any systemic treatment or treatment to the pelvis
  • Breastfeeding mothers
  • Mirena inserted greater than 12 weeks before randomisation/enrolment
  • Previous use of Mirena within the last 5 years from randomisation/enrolment
  • Contraindications to both Metformin and weight loss

Trial locations and contacts

17 sites in 2 countries.

17 sites in 2 countries

Australia13 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • The Wesley Hospital

    Auchenflower, Queensland, 4066

  • Royal Brisbane and Women's Hospital

    Brisbane, Queensland, 4029

  • Chris O'Brien Lifehouse

    Camperdown, New South Wales, 2050

  • Royal Women's Hospital

    Carlton, Victoria, 3053

  • Monash Medical Centre

    Clayton, Victoria, 3168

  • Greenslopes Private Hospital

    Greenslopes, Queensland, 4120

  • King Edward Memorial Hospital for Women

    Perth, Western Australia, 6008

  • Mater Health Services, Brisbane

    South Brisbane, Queensland, 4101

  • Mater Private Hospital

    South Brisbane, Queensland, 4101

  • Gold Coast Hospital

    Southport, Queensland, 4215

  • St John of God Hospital

    Subiaco, Western Australia, 6904

  • Townsville Hospital

    Townsville, Queensland, 4810

Other trials in Australia

New Zealand4 sites

  • Auckland City Hospital

    Auckland, 1023

  • Middlemore Hospital

    Auckland, 2025

  • Christchurch Women's Hospital

    Christchurch

  • Wellington Hospital

    Wellington

Other trials in New Zealand

About this study

Official title: A Phase II Randomised Clinical Trial of Mirena® ± Metformin ± Weight Loss Intervention in Patients With Early Stage Cancer of the Endometrium

Currently the standard treatment for early stage endometrial cancer or endometrial hyperplasia with atypia is a total hysterectomy (an operation to remove the uterus) and removal of both ovaries. While highly effective, this surgery carries significant side effects for:

  • young women who still wish to have children and would lose fertility; and
  • women with one or more disorders (or diseases) in addition to the early stage endometrial cancer or endometrial hyperplasia with atypia and/or morbid obesity who are at risk for surgical complications making surgery unsafe.
Read more

This study will access a new approach to the treatment of endometrial cancer to spare women of having to undergo major surgery that may be unwanted or unnecessary.

Mirena is approved in Australia for contraception, to treat heavy bleeding, and to prevent thickening of the lining of the uterus (endometrial hyperplasia) during oestrogen replacement therapy (HRT). However it is not approved to treat early stage endometrial cancer or endometrial hyperplasia with atypia. This research project will test to see if Mirena is an effective treatment for early stage endometrial cancer and endometrial hyperplasia with atypia.

Metformin is approved in Australia to treat Diabetes. However it is not approved to treat early stage endometrial cancer or endometrial hyperplasia with atypia. Therefore, it is an experimental treatment for early stage endometrial cancer and endometrial hyperplasia with atypia. This means that it must be tested to see if it is an effective treatment for early stage endometrial cancer and endometrial hyperplasia with atypia.

Weight loss interventions are feasible and safe, and already being implemented by gynaecologic oncologist to make women eligible for surgery. Weight loss of 7% body weight induces a large biological effect (for example reduces incidence of diabetes by 58%, and hypertension by 26%).

Being tested
Levonorgestrel, Metformin
Keywords
endometrial hyperplasia, endometrial adenocarcinoma, Gynecological Cancer
Medical subject headings
Endometrial Hyperplasia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LevonorgestrelDrug

    Also called Mirena

    Intrauterine device

  • MetforminDrug

    oral medication

Study groups in NCT01686126
Study groupRoleWhat they receive
Mirena + MetforminExperimentalMetformin tablets, 500mg twice daily orally, 6 months Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months
Receives: Drug: Levonorgestrel; Drug: Metformin
MirenaExperimentalLevonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months
Receives: Drug: Levonorgestrel
Mirena + Weight Loss InterventionExperimentalLevonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months Weight Loss Intervention will be delivered via Weight Watchers
Receives: Drug: Levonorgestrel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathological complete response

    Measured: 6 months

Secondary outcomes (1)

  1. Predict the response to treatment

    To predict the response to treatment through blood and tissue molecular biomarkers and to increase our molecular understanding of the biological pathogenesis of "early" EAC.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Sep 2012 (estimated)
  2. Study startDec 2012
  3. Primary completion3 Oct 2022
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
165 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01686126
Sponsor's protocol ID
feMMe
Acronym
feMMe
Status last verified
Aug 2024
First submitted
12 Sep 2012
Last updated
28 Aug 2024
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Baxter E, Robledo KP, Cummings M, Alizart M, Smith D, Obermair A. Central Pathology Review of Endometrial Hyperplasia and Adenocarcinoma Before and After Treatment With the Levonorgestrel Intrauterine Device-Results From the feMMe Phase 2 Randomized Clinical Trial. Am J Surg Pathol. 2026 Feb 1;50(2):259-266. doi: 10.1097/PAS.0000000000002492. Epub 2025 Nov 25.

    PubMed 41286566

  • Janda M, Robledo KP, Gebski V, Armes JE, Alizart M, Cummings M, Chen C, Leung Y, Sykes P, McNally O, Oehler MK, Walker G, Garrett A, Tang A, Land R, Nicklin JL, Chetty N, Perrin LC, Hoet G, Sowden K, Eva L, Tristram A, Obermair A. Complete pathological response following levonorgestrel intrauterine device in clinically stage 1 endometrial adenocarcinoma: Results of a randomized clinical trial. Gynecol Oncol. 2021 Apr;161(1):143-151. doi: 10.1016/j.ygyno.2021.01.029.

    PubMed 33762086

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Levonorgestrel and Metformin in people with Complex Endometrial Hyperplasia With Atypia and Grade 1 Endometrial Endometrioid Adenocarcinoma, run by Queensland Centre for Gynaecological Cancer at 17 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 28 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological complete response (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01686126, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2024.

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